Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer

Ovarian Cancer Clinical Trial

Official title:

A Phase 1/2 Single Arm Open-Label Clinical Trial of Gavocabtagene Autoleucel (Gavo-cel) in Patients With Advanced Mesothelin-Expressing Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03907852
• Other study ID #: TCR2-18-01
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 15, 2019
• Est. completion date: November 2, 2028

Study information

• Verified date: March 2024
• Source: TCR2 Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gavocabtagene autoleucel (gavo-cel; TC-210) is a novel cell therapy that consists of autologous genetically engineered T cells expressing a single-domain antibody that recognizes human Mesothelin, fused to the CD3-epsilon subunit which, upon expression, is incorporated into the endogenous T cell receptor (TCR) complex.

This Phase 1/2 study aims to establish the recommended Phase 2 dose (RP2D) and subsequently evaluate the efficacy of gavo-cel, with and without immuno-oncology agents, in patients with advanced mesothelin-expressing cancers, with overall response rate and disease control rate as the primary Phase 2 endpoints.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: November 2, 2028
• Est. primary completion date: November 2, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient is at least 18 years of age at the time the Informed Consent is signed.

• Patient has a pathologically confirmed diagnosis of either Malignant Pleural/Peritoneal Mesothelioma (MPM), Serous Ovarian Adenocarcinoma, Cholangiocarcinoma, or Non-Small Cell Lung Cancer (NSCLC) at screening.

• Patient's tumor has been pathologically reviewed by the central laboratory. For Serous Ovarian Adenocarcinoma, patients must have confirmed positive MSLN expression on >/= 30% of tumor cells that are 1+, 2+, and/or 3+ by immunohistochemistry (IHC). Ovarian patients will subsequently be stratified into two groups: high MSLN expression (>/= 50% of tumor cells that are 2+ and/or 3+) or low MSLN expression (>/= 30% of tumor cells that are 1+, 2+, and/or 3+ not meeting criteria for the high MSLN expression group). MPM patients must have MSLN expression of >/= 50% of tumor cells that are 2+ and/or 3+ by IHC. Cholangiocarcinoma and NSCLC patients must have MSLN expression of >/= 30% of tumor cells that are 1+, 2+, and/or 3+ by IHC.

• Prior to gavo-cel infusion, patients must have received at least 1 systemic standard of care therapy for metastatic or unresectable disease, with the exception of Cholangiocarcinoma patients who may have elected not to pursue standard frontline therapy. Regardless of tumor type, patients must not exceed 5 prior lines of therapy (excluding bridging therapy and surgical procedures). More details provided in the clinical protocol.

• Patient has an Eastern Cooperative Oncology Group performance status 0 or 1.

• Patient has a left ventricular ejection fraction > 45% as measured by resting echocardiogram, with no clinically significant pericardial effusion.

• Patient is fit for leukapheresis and has adequate venous access for the cell collection.

• Patient must have adequate organ function as indicated by the laboratory values in the clinical protocol

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Cholangiocarcinoma
• Cholangiocarcinoma Recurrent
• High Grade Ovarian Serous Adenocarcinoma
• Lung Neoplasms
• Mesothelioma
• Mesothelioma Peritoneum
• Mesothelioma, Malignant
• Mesothelioma; Pleura
• Mesotheliomas Pleural
• Non Small Cell Lung Cancer
• Non Small Cell Lung Cancer Metastatic
• Ovarian Cancer

Intervention

Biological:
• gavo-cel
gavo-cel

Drug:
• fludarabine
lymphodepletion chemotherapy
• cyclophosphamide
lymphodepletion chemotherapy
• Nivolumab
immuno-oncology agent
• Ipilimumab
immuno-oncology agent

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	National Cancer Institute	Bethesda	Maryland
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Duke University	Durham	North Carolina
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Miami Sylvester Cancer Center	Miami	Florida
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
TCR2 Therapeutics	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1- Primary Objective	Establish the recommended Phase 2 dose (RP2D) according to dose-limiting toxicity (DLT) of defined adverse events.	DLTs within 28 days post-treatment
Primary	Phase 2- Primary Objective	To evaluate the efficacy of autologous genetically modified T cells (gavo-cel), with or without immuno-oncology agents, in patients with MSLN-expressing unresectable, metastatic, or recurrent cancers as determined by overall response rate and disease control rate using RECIST v1.1 (or mesothelioma-specific RECIST criteria, if applicable).	ORR at 3 months; DCR based on ORR + SD lasting at least 8 weeks